The great desirability of grazing livestock upon alfalfa has long been known. The high protein content of that legume leads to enhanced weight gain in calves permitted to feed upon it. However, a great disadvantage exists. That is the tendency of alfalfa to cause bloat in ruminant stock, particularly cattle and sheep. The bloat is caused by the production and retention of an excess of frothy gas in the rumen, due to the microorganisms of the rumen and the high protein content of the alfalfa. (J. Quin, 1943, Onderstepoort J. Vet. Sci. 18:113 and Weiss, K. 1953, Onderstepoort J. Vet. Res. 26:241) If untreated, the pressure from the gas may accumulate in sufficient quantities to cause discomfort, and even death, by its interference with cardiovascular functions.
A number of chemicals have been tried in order to prevent and treat the frothy bloat. For example, emulsified oils were applied directly to the pasture by Johns and coworkers in New Zealand (A. Johns, N.Z.J. Sc. Tec. A. 36:289). This proved a semi-effective means of treating bloat but was not completely successful in that the oils were rapidly passed through the rumen and the reliability of the method was thus unsatisfactory.
In a seminal paper, Oxford (A. Oxford, N.Z.J. Agri. Res. 2:365) investigated the possible control of certain protozoa (Epidium ecaudatum) which were thought to contribute to bloat. It was further noted that the bloat retarding agent must not be lethal to friendly bacteria which are in the gut. In his paper Oxford points out that a particular class of neutral nonionic surface active agents consisting of straight chain polymers are interesting in this regard. In particular, he advocated the use of polyoxypropylene-polyoxyethylene block polymers at 80% polyoxypropylene and 20% polyoxyethylene.
In a later paper Reid, et al. (C. Reid, et al. N.Z.J. Agri. Res. 4:476 (1962)) carried out field tests using this compound and concluded that whereas such chemicals were useful in a gullet drench, they were not useful as an addition to the drinking water since due to "their bitter taste they are not suitable via drinking water".
Another important paper, Phillips (D. Phillips, N.Z.J. Agri. Res. 11:85 (1968)) concluded in his studies that a polyoxypropylene - polyoxyethylene polymer at 60% polyoxypropylene and 40% polyoxyethylene with a molecular weight of 2,900 was effective when mixed in the drinking water provided the cows were given time to become accustomed to the taste.
Along these lines, Bartley and Scott in their 1969 U.S. Pat. No. 3,465,083 argued that polyoxypropylene-polyoxyethylene block polymers at 67% polyoxypropylene and 33% polyoxyethylene with a total molecular weight of around 3,000, was both effective in controlling bloat and more palatable to the animal. They called this compound "poloxalene". In particular, in claims 6 and 7 of their patent they suggest the addition of the polymer to a molasses salt block ("Bloat Block") on the one hand and as a top dressing administered in granular form on the other. Other pertinent patents are U.S. Pat. Nos. 4,005,192 and 4,061,728, describing a block of reaction products of molasses, magnesium oxide and polyoxypropylene surface active compounds.
While the effectiveness of poloxalene has been demonstrated in many tests, substantial death losses have been associated with its use. In particular, many animals are not as interested in the "Bloat Block" or the poloxalene crumble, as are others, and they do not consume enough of the bloat retardant in order to enable them to safely graze the alfalfa foliage. Furthermore, the cost per animal is substantially higher than it should be since animals which do appreciate the molasses block may consume many times more per day than is required to control the bloat. This has the bad side effect of administering more of the chemical than one would like and, furthermore, it is a substantial economic disadvantage.
For these reasons it would be desirable to achieve a more uniform dosage in order to cut these substantial death losses, and provide a more economic administration of the bloat retardant.
Adding the poloxalene to drinking water would be an attractive solution to these problems. This would ensure a uniform and adequate consumption of the chemical by each animal since each animal drinks a consistent one gallon of water for one hundred pounds of body weight per day. However, the straight application of poloxalene to drinking water has several problems. The palatability of the material is a problem, as has been noted previously, and poloxalene is not easy to bring into solution. When added directly to the water it tends to gell and settle to the bottom of the water tank. In this latter context, Oakes, et al. (U.S. Pat. No. 4,407,780, Oct. 4, 1983) have pointed to previously used compositions as suffering from various disadvantages of gell formation, and lack of solubility which thus leads to difficulty when used under actual farming conditions. Furthermore, in the application of the bloat retarding chemical to drinking water, it is essential that the animals do not have access to other forms of drinking water since this would negate the benefits of the treated water. This is difficult to achieve in a farming operation of considerable size. For all these reasons, a carefully managed program is necessary in order to insure that the animals consume a proper quantity of the bloat retardant per day.
It would appear desirable to administer the bloat retardant by an indwelling reservoir which dispenses a controlled amount of the substance over a continuing period of time. Such devices are well-known in the medical, experimental and veterinary arts. See, for example, the book, Sustained Release Medications, J. C. Johnson, editor, Chemical Technology Review No. 177, Noyes Data Corporation, Park Ridge, N. J., 1980. That book describes patents issued between 1974 and 1980 related to the art under discussion. One such patent, U.S. Pat. No. 3,844,285, discloses an expanding indwelling dispenser for bloat control (page 401).
The present invention belongs to the class known as osmotic dispensing devices. Many such devices are discussed in the chapter "Osmotic Dispensing Devices" pp. 114-151, of the Johnson book described supra.
In an osmotic dispensing device, a dissolved substance is contained in a device carried within the animal to be treated with the situation. At least a portion of a wall of the device is a material such as a membrane permeable to an external fluid in the environment of use. The fluid diffuses through the membrane, and the resulting increase in pressure causes the dissolved substance to be expelled to the exterior of the device. Depending upon the mechanism used, zero order (constant) release rates can be achieved (see Johnson, pp. 114-115; U.S. Letters Pat. No. 3,845,770).
Hitherto such osmotic dispensing devices have not been appropriate for use in bloat control of livestock, for two primary reasons. The first is that the medication for bloat control is required to be dispersed for a much longer period of time and in greater amounts than in the usual application in order to be practical. The spent dispensing devices will thus need to be removed from the rumen. The second reason is that as the animal grows the bloat retardant must be released at a faster rate.
There is thus a need for osmotic dispensing devices which are large enough to be used for an extended period of time in livestock without needing frequent replacement, but can be removed at the end of that time, and which will dispense an increasing amount of medication as time passes.